Background: Pain management is a vital component of post-operative nursing care. Orthopedic patients in particular experience severe pain following surgical intervention. It was essential to explore the knowledge and clinical practice of nurses in orthopedic wards. Aim of the study: This study aimed to assess nurse's knowledge and practice regarding post-operative pain management for orthopedic patients. Design: A descriptive research design. Setting: The study was carried out in orthopedic department in (General governmental Hospital and El-Mabrra Health Insurance hospitals) in Port Said City/Egypt. Sample: A convenience sample of 50 nurses caring |for patients at orthopedic department, General governmental hospital (N=30), and El-Mabrra Health Insurance (N=20) in period of 6 months. Tools: -I) A Structured self-administered questionnaire that covering demographic data, and nurses' knowledge related to post-operative pain management for orthopedic patients (Tool II) Nurses' observational checklists. Results: the results revealed that60% of the studied nurses had unsatisfactory level of general knowledge, while 90% of them had unsatisfactory level of nurses' practice. Conclusion: There is lack of nurses' knowledge and practice regarding post-operative pain management for orthopedic patients. Recommendations: conducting educational and training programs to improve nurses' knowledge and practice regarding post-operative pain management for orthopedic patients.